Treatment of infectious diseases after organ transplantation using antigen-specific memory T cells in the peripheral blood

利用外周血中抗原特异性记忆T细胞治疗器官移植后的感染性疾病

基本信息

批准号：
17591349
负责人：
TANAKA Kazuo
金额：
$ 2.11万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Animal model : When the BALB/c mice bred under SPF condition were intra-peritoneally infected with 0.2LD50 of murine cytomegalovirus (MCMV), high frequencies of CD69^+/CD44^+ MCMV-specific CD8 T cells were noted in the lungs even at 6 to 12 months after infection (11.1±3.2% and 9.8±0.9%, respectively). In contrast, even though the viral load and expression levels of mRNA of such cytokines as IL-2, IL-7, IL-15 and IFN-γ in the lungs of MCMV-infected OF mice were comparable to those of infected SPF mice, the frequencies of MCMV-specific CD8 T cells in the lungs of infected GF mice were kept lower than 1% at 6 to 12 months after infection. In addition, the reconstitution of microbiota of MCMV-infected GF mice by orally administering a fecal suspension prepared from SPF mice restored both the frequencies of CD8^+/multimer^+ and CD8^+/multimer T cells to levels similar to those found in SPF mice. These results suggested the indigenous microbiota to play a crucial role in the expansion and m … More aintenance of viral specific CD8 memory T cells, probably by cross-reactivity between the antigenic epitope of the MCMV-specific memory T cells and the variety of peptides derived from the members of the microbiota. Such cross-reactivity may thus be a major feature of those cells. Then, we examined to adoptive transfer of the MCMV-specific CD8^+/multimer^+ memory T cells for the treatment of CMV disease, At first, we tried to in vitro expand the MCMV-specific CD8^+/multimer^+ memory T cells, by co-culture with the memory T cells with the antigen-pulsed dentritic cells and such cytokines as IL-2 and /or IL-15. However, we could not in vitro expand the memory T cells under this culture condition.Experiments using human materials : CMV-specific memory T cells were obtained from 20 volunteers, and then in vitro expansion of the memory T cells was done by co-culture with the memory T cells with the antigen-pulsed dentritic cells and IL-2. Memory T cells from the volunteer, who possessed the high frequency of CMV-specific memory T cells (>0.2% of total CD8 cells), could be adequately expanded. However, CMV-specific memory T cells form the other volunteers could not be expanded. Less

动物模型：当在SPF条件下繁殖的BALB/C小鼠被腹腔内感染0.2LD50的鼠巨细胞病毒（MCMV）时，在6至12个月的6至12个月中，CD69^+/CD44^+ MCMV特异性CD8 T细胞的CD69^+/CD44^+ MCMV特异性CD8细胞的高频在感染后（11.1.1.1.1.1; 9.2％＆9.2％）。相反，即使在感染的MCMV感染的MCMV肺中IL-2，IL-7，IL-15和IFN-γ等细胞因子的病毒载量和表达水平与感染的SPF小鼠的肺中的MCMV特异性CD8 T细胞的频率相当于受感染的GF肺部的MCMV特异性CD8 T细胞的频率，但在受感染的GF肺中受感染的频率低于1％。此外，通过口服从SPF小鼠制备的粪便悬浮液来重构MCMV感染的GF小鼠，这两个CD8^+/Multimer^+和CD8^+/Multimer T细胞的频率都与与SPF小鼠相似的水平相似。这些结果表明，土著菌群在扩展中起着至关重要的作用。因此，这种交叉反应性可能是这些细胞的主要特征。然后，我们检查了MCMV特异性CD8^+/Multimer^+内存T细胞的自适应转移，以治疗CMV疾病，首先，我们试图通过与抗原蛋白蛋白培养细胞和此类CyTokines和IL-1-1-1-1-1-1-1-1-1-l-1-1-l-1-1-l-1-l-1-l-1-l-1-l-cyly taste taste taste taste taste taste floks扩展了MCMV特异性CD8^+/多聚^+记忆T细胞。但是，我们无法体外扩展记忆T细胞在这种培养的条件下。使用人类材料的经验：CMV特异性记忆T细胞是从20名志愿者那里获得的，然后通过与抗原抑制的牙齿牙齿的牙本质细胞和IL-2共同培养来完成记忆T细胞的体外扩张。可以充分扩展的志愿者的记忆T细胞，他们拥有CMV特异性内存T细胞的高频（>> CD8总细胞的0.2％）。但是，CMV特异性内存T细胞形成其他志愿者无法扩展。较少的

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Therapeutic effect of a traditional Chinese medicine, ren-shen-yang-rong-tong, on nitric oxide mediated lung injury in a mouse infected with murine cyteomegalovirus

中药“仁肾养荣通”对小鼠巨细胞病毒感染一氧化氮介导的肺损伤的治疗作用

DOI：
发表时间：
2006
期刊：
International Immunopharmacology 6
影响因子：
0
作者：
Takahashi A;Sato Y;Shiomi Y;et al.;Tanaka et al.
通讯作者：
Tanaka et al.

Cytomegalovirus MCK-2 controls mobilization and recruitement of myeloid progenitor cells to facilitate dissemination

巨细胞病毒 MCK-2 控制骨髓祖细胞的动员和募集以促进传播

DOI：
发表时间：
2006
期刊：
Blood 107
影响因子：
0
作者：
Kasahara M;Ueda M;Haga H;Hiramatsu H;Kobayashi M;Adachi S;Sakamoto S;Oike F;Egawa H;Takada Y;Tanaka K;Noda et al.
通讯作者：
Noda et al.

医学大辞典(第19版)

医学词典（第19版）